1. count the defenders ( how many on the left , right, middle near the line of scrimmage ) choose the weakest area and attack.
2. choose appropiate run play. power O is nice , zone stretches are good, tosses and counters are very high risk high reward. I have a counter in my audibles and only use it when the d is over compensating.
3. be aware of your quick audibles and field position. never come out in a run that is your quick run audible even if you are going to run that play , pick a different one and audible to it. flip the play to give you the wide side of the field, not always as it can be a tell as to which way you are running, but sometimes the extra few yards can help you turn that corner.
4. keep the D honest. pass out of your run formations. maybe a screen or a pa or just a good pass. find a play you are comfortable with and run it every now and then. Heck even a quick pass audible with a hot routed streak, slant, drag combo will keep them thinking on their toes.
5. change it up. run out of your pass formations. draws and handoffs out of the gun can be effective it used correctly.
6. find a way to use motion to get a extra blocker against zone.. if the D is running zone motioning a wr to block at the point of attack or to seal the edge can be very effective. also this can give you a good man zone read if you are passing.
Portal 
